Abstract 46: MIND Diet-Related Transcriptomic Alterations in the Aging Human Brain is Associated With Lower Dementia Risk and Slower Cognitive Decline

Abstract

Background: Healthy diets are associated with lower dementia risk; however, the underlying molecular mechanisms are largely unknown. Hypothesis: A healthy diet is associated with brain transcriptomic alterations that are related to a better cognitive health. Methods: RNA sequencing was conducted using dorsolateral prefrontal cortex from 1,204 deceased participants of the Religious Orders Study and Rush Memory and Aging Project. Annual cognitive/clinical assessments were performed from enrollment through death. Diet was assessed at baseline/follow-ups in 482 individuals using a validated food-frequency questionnaire. Among these individuals, we calculated a MIND diet score ( M editerranean-DASH Diet I ntervention for N eurodegenerative D elay) to assess intakes of a presumed neuroprotective diet pattern, and applied elastic net regression to identify a brain transcriptomic profile associated with the MIND diet. Results: In individuals with dietary data (n=482), we identified a transcriptomic profile, consisting of 50 genes, for the MIND diet; the profile score was significantly correlated with MIND diet score ( r =0.15; P =0.001). In multivariable analyses of the remaining 722 independent individuals, a higher transcriptomic profile score was significantly associated with lower odds of dementia (OR=0.76 per SD increment in transcriptomic score; P =0.003) and slower annual rate of decline in global cognition (β=0.011; P =0.004). In secondary Mendelian randomization analysis, genetically predicted MIND diet-transcriptomic profile score was associated with lower Alzheimer’s dementia risk (OR=0.93; P =0.04), but not vice versa. Conclusion: MIND diet was associated with gene expressions in the human brain that were related to less dementia and cognitive decline. Associations did not appear due to reverse causation. Our findings suggest that associations between diet and brain health may involve molecular alterations at the transcriptomic level; and may inform future therapeutics design for dementia prevention.